Genetic aberrations and survival in plasma cell leukemia

Abstract

Plasma cell leukemia (PCL) is an aggressive and rare hematological malignancy that originates either as primary disease (pPCL) or as a secondary leukemic transformation (sPCL) of multiple myeloma (MM). We report here the genetic aberrations and survival of 80 patients with pPCL or sPCL and make comparisons with 439 cases of MM. pPCL presents a decade earlier than sPCL (54.7 vs 65.3 years) and is associated with longer median overall survival (11.1 vs 1.3 months; P<0.001). 14q32 (IgH) translocations are highly prevalent in both sPCL and pPCL (82-87%); in pPCL IgH translocations almost exclusively involve 11q13 (CCND1), supporting a central etiological role, while in sPCL multiple partner oncogenes are involved, including 11q13, 4p16 (FGFR3/MMSET) and 16q23 (MAF), recapitulating MM. Both show ubiquitous inactivation of TP53 (pPCL 56%; sPCL 83%) by coding mutation or 17p13 deletion; complemented by p14ARF epigenetic silencing in sPCL (29%). Both show frequent N-RAS or K-RAS mutation. Poor survival in pPCL was predicted by MYC translocation (P=0.006). Survival in sPCL was consistently short. Overall pPCL and sPCL are different disorders with distinct natural histories, genetics and survival.

Figure 1

Overall survival (OS) in pPCL and sPCL. (a) OS in PCL showing superior survival of pPCL vs sPCL from the time of leukemia diagnosis. (b) OS in pPCL stratified by initial treatment with multiagent chemotherapy (VAD or VBMCP), MP, or no treatment. The survival of patients treated with multiagent chemotherapy and SCT is also shown. (c) OS in sPCL stratified by treatment with combination chemotherapy (VAD, VBMCP or VBAP), MP or no treatment MP, melpahalan and prednisone; PCL, plasma cell leukaemia; pPCL, primary PCL; SCT, stem cell transplant; sPCL, secondary PCL.